Open AccessMutation analysis and clinical characterization of Iranian patients with mucopolysaccharidosis type I
Author(s) -
Taghikhani Mohammad,
Khatami Shohreh,
Abdi Mohammad,
Hakhamaneshi Mohammad Said,
Alaei Mohammad Reza,
Zamanfar Daniel,
Vakili Rahim
Publication year - 2019
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.22963
Subject(s) - mucopolysaccharidosis type i , missense mutation , sanger sequencing , exon , mutation , genetics , gene , genotype , allele , biology , mutation testing , medicine , disease , pathology , enzyme replacement therapy
Abstract Background Mucopolysaccharidosis type I (MPSI) is a rare autosomal recessive disorder caused by a deficiency of α‐ l ‐iduronidase (IDUA) encoded by the IDUA gene. We examined the mutation spectrum of the IDUA gene to explain the clinical, biochemical, and molecular features in 21 Iranian patients with MPSI. Methods Sanger sequencing was used to measure the IDUA gene sequence in the coding region and exon‐intron boundaries. We recorded the clinical findings of studied patients at the first diagnosis of disease and then during the treatment and follow‐up. Results Five different missense disease‐causing mutations were determined in our patient groups, indicating 90.48% of detection rate. The most widespread mutation was the p.Y109H, occurring in 15.625% of all alleles, which was reported for the first time in our study. Other frequent mutations were as follows: p.Ser157Pro (12.5%), p.Gly84Arg (12.5%), p.Asp257His (9.375%), and p.Asp301Glu (9.375%). Three ones of them were new missense mutations: p.Ser157Pro, p.Asp257His, and p.Asp301Glu. Discussion The results of this study explain the different spectrum of IDUA gene mutations in our patients with MPSI. We introduced here 32 different variants including four new variants: p.Y109H (15.625%), p.S157P (12.5%), p.D257H (9.375%), and p.D301E (9.375%). In this series, there was no relationship between the happening of clinical features and genotype variations and biochemical findings.